Implications of apoptosis regulators in tumorigenesis

The process of cell loss and cell gain is homeostatically balanced in order to not only generate and maintain the complex dynamic architecture of tissues, but also to allow adaptation to changing circumstances. Tumor cells survive only by virtue of mutations that allow them to proliferate and to evade death signals. In fact, defects in the programd cell death inducing pathways contribute to neoplastic transformation, progression and metastasis by creating a permissive environment for genetic instability and accumulation of gene mutation. Resistance to apoptosis can also enhance the escape to tumor cells from surveillance by the immune system. Moreover, because chemotherapy and irradiation act mostly by inducing apoptosis, dysregulation in the apoptostic pathway can make cancer cells resistant to therapy. This review gives an update on the key players involved in apoptosis as well as how pathologic alterations in each step of apoptotic pathways are involved in the entire progression of neoplastic transformation, how impaired apoptosis affects therapy and how direct targeting vs. the apoptotic regulators could lead to more effective treatment of cancer.